Outline

Objective: Genetic instability, genomic hypomethylation and epigenetic silencing through promoter DNA hypermethylation are hallmarks of cancer development and progression. The methionine metabolism plays a central role in DNA synthesis and repair, and DNA methylation. Several functional polymorphisms of methionine metabolism have been associated with an increased incidence of various human cancers. The authors have investigated whether such associations may also exist for brain tumors.

Results: In GBM, PCNSL and meningioma WHO grade III patients the G-allele of MTR c.2756A>G was significantly under-represented (GBM: p<0.001; PCNSL: p<0.005; meningioma WHO III: p=0.001), suggesting a protective effect of the G-allele in malignant brain tumors. In addition, we found an association between meningiomas (all WHO grades) and the CBS844ins68 polymorphism (p=0.01).

Conclusions: Our data suggest a role for functional genetic variants of methionine metabolism and therefore variations of methionine metabolism in a more general sense in the pathogenesis of brain tumors. Nutritional intake is a key determinant of methionine metabolism. Hence, nutritional measures may influence the risk to develop certain brain tumors.